The immune system is highly complex and tightly regulated, with many alternative pathways capable of compensating for deficiencies in other parts of the system. There are however occasions when the immune response becomes a cause of disease or other undesirable conditions if activated. Immunoinflammatory disorders are thus characterized generally by the inappropriate activation of the body's immune defenses. Rather than targeting infectious invaders, the immune response targets and damages the body's own tissues or transplanted tissues. Such diseases or undesirable conditions are for example autoimmune diseases, graft rejection after transplantation, or allergy to innocuous antigens, psoriasis, chronic inflammatory diseases such as atherosclerosis, and inflammation in general.
The tissue targeted by the immune system varies with the disorder. For example, in multiple sclerosis, the immune response is directed against the neuronal tissue, while in Crohn's disease the digestive tract is targeted. Immunoinflammatory disorders affect millions of individuals and include conditions such as asthma, allergic intraocular inflammatory diseases, rheumatoid arthritis, atopic dermatitis, atopic eczema, type I diabetes, hemolytic anemia, inflammatory dermatoses, inflammatory bowel or gastrointestinal disorders (e.g., Crohn's disease and ulcerative colitis), multiple sclerosis, myasthenia gravis, pruritis/inflammation, psoriasis, cirrhosis, and systemic lupus erythematosus.
In these cases and others involving inappropriate or undesired immune response there is a clinical need for immunosuppression. The pathways leading to these undesired immune responses are numerous and in many cases are not fully elucidated. However, they often involve a common step, which is activation of lymphocytes.
Current treatment regimens for immunoinflammatory disorders typically rely on immunosuppressive agents that often are non-specific in their activity. The effectiveness of these agents can vary and their use is often accompanied by adverse side effects. Thus, improved therapeutic agents having specificity for inhibiting activation of T lymphocytes and methods for the treatment of immunoinflammatory disorders are needed.